Bis-chromonyl compounds are pharmacologically active compounds in which two moieties structurally related to chromone are linked together, often through a methylene-containing bridge. The chemical structure of chromone is shown below.

One of the best known bis-chromonyl compounds is cromolyn sodium (sometimes referred to as “cromoglycate”), which is disodium 5,5′-((2-hydroxytrimethylene)dioxy)bis(4-oxo-4H-1 benzopyran-2-carboxylate). Cromonlyn sodium has been reported to inhibit mast cell degranulation of monkey gingiva. See Nuki et al. (1975) J. Periodontal. Res. 10:282-287. As such, cromolyn sodium is often used as an inhaled anti-inflammatory agent for the preventive management of asthma.
Marketed forms of cromolyn sodium include the following: RYNACROM® and NASALCROM® brands of cromolyn sodium nasal spray for allergic rhinitis; INTAL® brand of cromolyn sodium inhaler for preventive management of asthma; OPTICROM®, OPTREX ALLERGY® and CROLOM® brands of cromolyn sodium eye drops for allergic conjunctivitis; and GASTROCOM® brand of cromolyn sodium for the treatment of mastocytosis, dermatographic urticaria, and ulcerative colitis.
Cromolyn (in contrast to cromolyn sodium) and other non-salt forms of bis-chromonyl compounds are poorly absorbed from the gastrointestinal tract, often with no more than 1% of an administered dose being absorbed by humans following oral administration, the remainder being excreted in the feces. As such, it would be advantageous to (among other things) improve the overall oral bioavailability of bis-chromonyl compounds.
The present invention seeks to address this and other needs in the art by providing (among other things) a conjugate of a water-soluble and non-peptidic oligomer and bis-chromonyl compound.